Haemofiltration Study : IVOIRE (hIgh VOlume in Intensive Care)

Shock, Septic Clinical Trial

— IVOIRE  

Official title:

Impact of High-volume Veno-venous Continuous Hemofiltration in the Early Management of Septic Shock Patients With Acute Renal Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00241228
• Other study ID #: 9410-04
• Secondary ID: 2004-024
• Status: Completed
• Phase: N/A
• First received: October 17, 2005
• Last updated: October 12, 2010
• Start date: October 2005
• Est. completion date: October 2010

Study information

• Verified date: October 2010
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

Sepsis and septic shock are still important causes of mortality in intensive care medicine. Renal replacement therapy by standard volume haemofiltration is currently used, but a higher-volume haemofiltration may improve the prognosis. The study is a prospective randomized multicenter trial comparing two treatments in patients suffering from septic shock complicated with acute renal failure admitted to ICU. One group will be treated by early high volume haemofiltration (70 ml/kg/h) and the second group by standard volume haemofiltration (35 ml/kg/h). The main outcome will be one-month mortality.

Description:

Background

Sepsis and septic shock are still important causes of mortality in intensive care medicine nowadays. Mortality ranges from 40 up to 80 % depending on the number of organ failures. Therapeutic strategy consists of two major components: haemodynamic stabilization with restoration of adequate arterial pressure and optimization of peripheral perfusion delivery, and infection treatment. Mortality remains high despite the use of new antimicrobial therapy and adjuvant therapies such as activated protein C, low dose corticoids and haemofiltration. Initial observations in patients with acute renal failure treated by haemofiltration showed azotemia control, restoration of the sodium-water balance, elimination of inflammatory mediators and improvement of the cardiac and pulmonary functions was demonstrated independently of a negative water balance. There is no human randomized study so far demonstrating these preliminary findings. Nevertheless, several authors have demonstrated inflammatory mediators elimination by the use of haemofiltration. Moreover, the clinical improvement seems to be related to the ultra filtration dose and to the early initiation of therapy. Joannes-Boyau et al carried out a pilot study in abdominal surgery patients demonstrating that the use of high volume haemofiltration in patients with septic shock and multiple organ failure restores hemodynamic stability with drastic reductions in catecholamine requirements and a substantial reduction of observed vs. expected mortality.

Objectives

The principal objective of the study is to evaluate the effect of early Continuous High Volume Haemofiltration on 28-day mortality in patients with septic shock complicated by acute renal failure. The secondary objectives are to assess the effect of High Volume Haemofiltration on haemodynamics, doses of catecholamines, organ failures, duration of mechanical ventilation, duration of renal replacement therapy need, morbidity, length of ICU and hospital stay, and 60- and 90-day mortality.

Study design

Open label randomized multicenter controlled trial on two parallel groups of patients with septic shock and acute renal failure admitted to ICU, treated early either by high volume (70 ml/kg/h) or by standard volume (35 ml/kg/h) haemofiltration.

Eligibility criteria

Inclusion criteria. Septic shock (Bone criteria) for less than 24 hours, RIFLE criteria :

injury or worse, age over 18 years, and written informed consent by next of kin. Non inclusion criteria. Cirrhosis, age over 80 years, life expectancy less than 3 months or metastatic cancer.

Intervention

High volume (70 ml/kg/h) vs. standard volume (35 ml/kg/h) haemofiltration during 96 hours. Further renal replacement therapy (if haemofiltration, only standard volume is allowed) may be used according to investigator decision.

Primary endpoint

All cause 28-day mortality.

Statistical aspects

460 patients are planned to be included (230 in each group). A 15 % absolute reduction in 28-days all-cause mortality in the high volume group compared with the standard group is expected. However, as this reduction might be greater, an interim analysis is planned when half of the total sample size will have been included. Data will be analyzed on an intention-to-treat basis.

Duration of the study: 3 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 139
• Est. completion date: October 2010
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• septic shock (Bone criteria) for less than 24 hours

• RIFLE criteria : injury or worse

• age over 18 years

• written informed consent by next of kin.

Exclusion Criteria:

• cirrhosis

• age over 80 years

• life expectancy less than 3 months or metastatic cancer

• for women : pregnancy and breastfeeding

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Kidney Injury
• Renal Failure, Acute
• Renal Insufficiency
• Shock, Septic

Intervention

Device:
• Venovenous haemofiltration (renal replacement therapy)
High Volume ultra filtration (70 ml/kg/h)
• Venovenous haemofiltration (renal replacement therapy)
Conventional Volume (35 ml/kg/h)

Locations

Country	Name	City	State
Belgium	Cliniques de l'Europe	Bruxelles
Belgium	Astrid Queen Military Hospital	Bruxelles (Neder Over Hembeek)
Belgium	TIVOLI Hospital	La Louviere
Belgium	University Hospital	Liege
Belgium	St-Pierre Para-University Hospital	Ottignies-Louvain-La-Neuve
France	Hospital	Agen
France	Clinic Bordeaux Nord	Bordeaux
France	University Hospital	Brest
France	University Hospital	Grenoble
France	Hospital R Boulin - Libourne	Libourne
France	University Hospital	Lyon
France	Aphp - Hegp	Paris
France	Service d'Anesthésie-Réanimation II, Groupe Hospitalier Sud, CHU de Bordeaux	Pessac
France	Hospital	Tourcoing
Netherlands	Hospital	Delf
Netherlands	Hospital	Heerlen

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Bordeaux	Ministry of Health, France

Countries where clinical trial is conducted

Belgium,  France,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	all-cause mortality.		28-day	Yes
Secondary	Haemodynamic parameters and volume loading		Every 12 hours during 96 hours after inclusion	Yes
Secondary	Doses and duration of catecholamine infusions		Every 12 hours during 96 hours after inclusion	Yes
Secondary	Organ failures		During 96 hours after inclusion	No
Secondary	Duration of mechanical ventilation		Total during the stay in intensive care	No
Secondary	Duration of renal replacement therapy		Total during the stay in Intensive Care Unity (ICU)	No
Secondary	Morbidity		Total during the stay in intensive care	No
Secondary	Length of stay in ICU and hospital		End of hospitalization	No
Secondary	Mortality		in ICU (96 first hours after inclusion), 60 and 90-day	No